Programmable molecular manipulating processes

ABSTRACT

A system manipulates molecules using a set of proximal probes such as those used in atomic force microscopes. An electrostatic pattern is placed on a set of proximal probes such that each proximal probe may exert an electrostatic force. A molecule is captured using those electrostatic forces, after which the molecule can be manipulated while the molecule remains captured by the proximal probes. The electrostatic pattern can be modified such that the molecule moves and/or rotates over the set of proximal probes while the molecule remains captured by the set of proximal probes. The electrostatic pattern can be used to bend or split the molecule while the molecule remains captured by the set of proximal probes, thereby allowing the system to engage the molecule in chemical reactions, e.g., to act as a synthetic catalyst or a synthetic enzyme.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is related to the following application:application Ser. No. 10/965,173, filed (concurrently herewith), entitled“Programmable molecular manipulating devices”, which is herebyincorporated by reference.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to usage of proximal probes ofatomic-scale precision for interactions with molecules.

2. Description of Related Art

Research discoveries continue to advance the knowledge ofnanotechnology. Scientists are venturing into the realm of the almostindescribably tiny. In nanotechnology, everything can be described interms of atomic interactions. At these dimensions, the distinctionsbetween biology and physics are blurring, which increases the difficultyof nanotechnology because, despite the number of advances, scientists intheir respective disciplines are encroaching upon each other's researchdomains. For example, to make tiny electronic circuits, some physicistshave tried to mimic nature by causing inanimate matter to assembleitself in a manner that resembles biological processes.

The manipulation of matter at the atomic level is not new. In 1981, GerdBinnig and Heinrich Rohrer at the IBM Research Laboratory in Zurich,Switzerland, invented and patented the scanning tunneling microscope(STM) (U.S. Pat. No. 4,343,993, herein incorporated by reference in itsentirety for all purposes), which greatly advanced the ability tounderstand the microscopic world at the atomic level. The key componentof an STM is an extremely sharp tip made from a metal such as tungstenmounted on an array of piezoelectric elements which control the tip'sposition in three dimensions. The STM can spatially control the tip veryprecisely, such as on the order of a nanometer with respect to asurface. At such tiny distances, currents can tunnel between the tip andthe surface. As the tip is moved across the surface of the sample, itsheight is adjusted to keep the tunneling current at a constant amountsuch that the STM can image the electron clouds of the surface atoms inthe sample. With pictures of the surface of inorganic materials such asmetal and semiconductors, the STM gave scientists their first vision ofthe nanoworld. This work won Binnig and Rohrer the Nobel prize in 1986.

Despite its capabilities, the STM is limited to imaging conductingmaterials. To overcome this limitation, Binnig and others developed arelated device to the STM called an atomic force microscope (AFM). Thisnow well-known device senses the topography of a sample using a tiny tipmounted on the end of a minuscule, microfabricated cantilever. Ratherthan using the tunneling current, the sample is scanned by actuallybringing the tip in contact with the sample surface, and the interactionof atomic forces between the nanometer-sharp tip and the sample surfacecauses pivotal deflections of the cantilever. The AFM measures theminute upward and downward deflections needed to maintain a constantforce of contact. As the AFM relies on contact force, it can be used toimage nonconducting materials such as organic or insulating materials.

Other variants of the STM and AFM have been developed. These devices canprobe other aspects of materials at the molecular level such as magneticand electrostatic forces, van der Waals interactions, temperaturevariations, optical absorption, near-field optics, and acoustics. Theseare collectively known as “proximal probes”; a variety of these probesare described in Pool, “Children of the STM”, Science, v. 247, pp.634–636 (1990).

As soon as scientists could see individual atoms, they could not resistplaying with them. Proximal probe devices have been used to manipulateatoms and molecules essentially by picking them up with the scanning tipand moving them; e.g., see D. M. Eigler and E. K. Schweizer,“Positioning Single Atoms with a Scanning Tunneling Microscope”, Nature,v. 344, pp. 524–526 (1990), which describes the positioning of xenonatoms on a nickel substrate to form the initials “IBM”. Other STM imagescan be found in “STM Rounds Up Electron Waves at the QM Corral”, PhysicsToday, v. 46, n. 11, pp. 17–19 (1993).

IBM and others have developed new applications for proximal probestechnologies. With a team of colleagues in Zurich, Binnig has created ananoscopic brush with over a thousand tiny tips, each on its owncantilever, in a “millipede” storage system. Using heater cantilevers,dents are made in a polymer material; such thermomechanical recordinghas been demonstrated at 400 gigabytes per square inch storage density.The tips are used for reading the dents as well; data rates of a fewmegabytes per second for reading and 100 kilobytes per second forwriting have been demonstrated, as described in Binnig et al.,“Ultrahigh-density Atomic Force Microscopy Data Storage with EraseCapability”, Applied Physics Letter, v. 74, n. 9, pp. 1329–1331, Mar.01, 1999, and Vettinger et al., “The Millipede—More Than One ThousandTips for Future AFM Data Storage”, IBM Journal of Research &Development, v. 44, n. 3, pp. 323–340, May 2000. A magnetic millipedewhich uses a magnetic substrate is described in Allenspach et al., U.S.Pat. No. 6,680,808, “Magnetic Millipede for Ultra High Density MagneticStorage”, herein incorporated by reference in its entirety for allpurposes.

While most of Binnig's work has been based on mechanical principles,others are using natural processes for insights on how to manipulatematter. Angela Belcher at the University of Texas has used proteins tobuild new semiconductor materials. As an example, she studied abaloneshell, which despite being made of two types of chalk, is about 3000times as strong as the chalk found in rock; it is proteins produced bythe abalone's RNA which determine how to optimally arrange the chalkmolecules. Using this insight, she has assembled a set of proteins whichcontrol crystal growth in various ways. Some of this research isdescribed in “Selection of Peptides with Semiconductor BindingSpecificity for Directed Nanocrystal Assembly”, Nature, v. 405, pp.666–668 (8 Jun. 2000).

Like Belcher, Heller et al. has used chemical chains to interact withother molecules, as described in U.S. Pat. No. 5,605,662, “ActiveProgrammable Electronic Devices for Molecular Biological Analysis andDiagnosis”. In Heller et al., the chains are held in place by an arrayof microlocations (much larger than individual molecule size) which areset up to hold different chemical agents at each site which in turn bindto the molecules of interest. While this permits interestingprogrammability of what molecules are concentrated in which area, itdoes not manipulate the molecules individually but rather in bulk.Belcher and Heller et al. do not directly manipulate the molecules butrather indirectly affect the molecules using analytes, proteins, ortheir equivalents.

Researchers have also proposed combining the selection qualities oforganic molecules and the positioning precision of proximal probes. EricDrexler in Nanosystems: Molecular Machinery, Manufacturing, andComputation, Wiley Interscience (1992), proposed an AFM having multiplebead bound worksites comprising organic molecules on the probe surface.Harold Craighead and his team at Cornell University have attachedantibodies to a proximal probe on a cantilever. With this device, theycan detect the presence of particular bacteria. If present, theantibodies bond to the bacteria; as the probe is weighed down by theaccumulation of bacteria, the resonant frequency of the vibratingcantilever is changed.

In living beings, most manipulations are driven by DNA, RNA, and specialproteins which work on the principle of creating an electrostaticpattern of charges which closely match the complementary pattern ofcharges on the molecule to be manipulated, thereby allowing theappropriate molecule to be attached to an enzyme, catalyst, or othermanipulating molecule. It would be advantageous to provide the abilityto perform similar types of molecular manipulation using proximal probetechnology.

SUMMARY OF THE INVENTION

A method, an apparatus, a system, and a computer program product arepresented for manipulating molecules using a set of proximal probes,such as the proximal probes used in atomic force microscopes,electrostatic force microscopes, scanning tunneling microscopes, and thelike. An electrostatic pattern is placed on a subset of two or moreproximal probes in the set of proximal probes such that an end portionof each proximal probe in the subset of proximal probes exerts anelectrostatic force. A molecule is captured using the electrostaticforces that are exerted by the electrostatic pattern, after which themolecule can be manipulated while the molecule remains captured by theset of proximal probes. The electrostatic pattern is modified to createa different electrostatic pattern on a different subset of two or moreproximal probes in the set of proximal probes such that the moleculemoves and/or rotates over the set of proximal probes while the moleculeremains captured by the set of proximal probes. The electrostaticpattern can be used to bend or split the molecule while the moleculeremains captured by the set of proximal probes, thereby allowing thesystem to engage the molecule in chemical reactions, e.g., to act as asynthetic catalyst or a synthetic enzyme.

One or more sets of proximal probes may also be mechanically and/orelectrically manipulated as a group. As a set of proximal probes ismanipulated, a captured molecule is moved with the set of proximalprobes, thereby causing modifications to the captured molecule throughmechanical actions or through chemical reactions.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features believed characteristic of the invention are setforth in the appended claims. The invention itself, further objectives,and advantages thereof, will be best understood by reference to thefollowing detailed description when read in conjunction with theaccompanying drawings, wherein:

FIG. 1 depicts a block diagram that shows a data processing system forcontrolling a proximal probe array block in accordance with anembodiment of the present invention;

FIG. 2 depicts a diagram that shows a proximal probe with a conductivemicrotip for use in an implementation of the molecular manipulationsystem of the present invention;

FIG. 3 depicts a diagram that shows a manner for forming aglass-insulating proximal probe with a conducting microtip for use in animplementation of the molecular manipulation system of the presentinvention;

FIG. 4 depicts a diagram that shows a proximal probe with a cantileverhaving a conductive microtip for use in an implementation of themolecular manipulation system of the present invention;

FIG. 5 depicts a block diagram that shows a group of proximal probesthat are assembled together to form a proximal probe array block inaccordance with an embodiment of the present invention;

FIG. 6 depicts a diagram that shows a one-dimensional proximal probearray that is presenting an electrostatic pattern which is facing theelectron cloud of a captured molecule in accordance with an embodimentof the present invention;

FIG. 7 depicts a diagram that shows a frontal, edge-on view of aone-dimensional proximal probe array block in accordance with anembodiment of the present invention;

FIG. 8 depicts a diagram that shows a two-dimensional proximal probearray that can present an electrostatic pattern for attempting tocapture a targeted molecule that exhibits an electron cloud thatcontains polarized locations in accordance with an embodiment of thepresent invention;

FIG. 9 depicts a diagram that shows a frontal, edge-on view of atwo-dimensional proximal probe array block in accordance with anembodiment of the present invention;

FIG. 10 depicts a diagram that shows a single row of a two-dimensionalproximal probe array that is presenting an electrostatic pattern whichis facing the electron cloud of a captured molecule in accordance withan embodiment of the present invention;

FIG. 11 depicts a diagram that shows a pair of juxtaposedtwo-dimensional proximal probe array blocks that can be used to capturea targeted molecule in accordance with an embodiment of the presentinvention;

FIG. 12 depicts a diagram that shows a pair of opposing two-dimensionalproximal probe array blocks that can be used to capture a targetedmolecule in accordance with an embodiment of the present invention;

FIG. 13 depicts a flowchart that shows a process for using proximalprobe arrays to manipulate molecules in accordance with an embodiment ofthe present invention;

FIG. 14 depicts a diagram that shows a proximal probe array block thatis attempting to capture and hold one of a set of targeted moleculesthat are deposited as a film on a surface;

FIGS. 15A–15D depict a set of diagrams that show a method of using aproximal probe array to shift an electrostatic pattern over a shortperiod of time in accordance with an embodiment of the presentinvention;

FIG. 16A depicts a diagram that shows a method for using a proximalprobe array block to move a targeted molecule in accordance with anembodiment of the present invention;

FIG. 16B depicts a diagram that shows a method for using a proximalprobe array block to bend or flex a targeted molecule in accordance withan embodiment of the present invention;

FIG. 16C depicts a diagram that shows a method for using a proximalprobe array block to twist or pivot a portion of a targeted molecule inaccordance with an embodiment of the present invention;

FIG. 16D depicts a diagram that shows a method for using a proximalprobe array block to break a targeted molecule in accordance with anembodiment of the present invention;

FIG. 17 depicts a diagram that shows a method for using a proximal probearray to create a molecule by combining two targeted molecules inaccordance with an embodiment of the present invention;

FIG. 18 depicts a diagram that shows a method for using multipleproximal probe arrays to create a molecule by combining two targetedmolecules in accordance with an embodiment of the present invention;

FIG. 19 depicts a diagram that shows a pair of cantilevered tips at theends of proximal probes on a proximal probe array in which the tips areflexed to split a captured molecule in accordance with an embodiment ofthe present invention;

FIG. 20 depicts a diagram that shows a pair of juxtaposed proximal probearray blocks in which the proximal probe array blocks are moved to splita captured molecule in accordance with an embodiment of the presentinvention;

FIG. 21 depicts a diagram that shows a pair of opposing proximal probearray blocks in which the proximal probe array blocks are moved to splita captured molecule in accordance with an embodiment of the presentinvention;

FIG. 22 depicts a diagram that shows a pair of opposing proximal probearray blocks in which one of the proximal probe array blocks is moved toflex a captured molecule in accordance with an embodiment of the presentinvention;

FIG. 23 depicts a diagram that shows a method for using a proximal probearray block to manipulate a targeted molecule in which the proximalprobe array block has a self-contained modification mechanism inaccordance with an embodiment of the present invention; and

FIGS. 24A–24I depicts a set of diagrams that show multiple molecularmanipulations using a proximal probe array block in accordance with anembodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

With reference now to FIG. 1, a block diagram depicts a data processingsystem for controlling a proximal probe array block in accordance withan embodiment of the present invention. In contrast to prior art usageof proximal probes, the present invention employs a set of two or moreproximal probes in programmable molecular manipulation system 100; anarrangement of proximal probes is termed a “proximal probe array”. In apreferred embodiment, a set of proximal probes are aligned in a regularor uniform manner to form an array of proximal probes; in an alternativeembodiment, the set of proximal probes may have irregular spacing orinter-probe gaps. The exemplary figures herein depict a proximal probeas a tetrahedron, but the present invention may be implemented usingproximal probes of different shapes and sizes. For example, a type ofproximal probe is disclosed in Bayer et al., “Micromechanical sensor forAFM/STM profilometry”, U.S. Pat. No. 6,091,124, issued Jul. 18, 2000,herein incorporated by reference in its entirety for all purposes; adifferent type of proximal probe is disclosed in Doezema et al.,“Silicided silicon microtips for scanning probe microscopy”, U.S. Pat.No. 6,198,300, issued Mar. 06, 2001, herein incorporated by reference inits entirety for all purposes. As another example, each proximal probemay comprise at least one buckytube or nanotube form of carbon, siliconnanotube, or a nanotube that is made of some other element, as well aspolymers.

An assembly of proximal probes 102 forms proximal probe array block(s)104, which may include supporting structure and/or supporting circuitryin addition to the proximal probes themselves; an embodiment of thepresent invention may employ a plurality of proximal probe array blocks,each of which is associated with one or more actuator(s)/servo(s) 106such that a proximal probe array block can be translated in at least onespatial dimensional but preferably three spatial dimensions as well asrotated about the three spatial axes. It should be noted that thefigures that are described herein are not drawn to scale.

Computer 108 sends commands to actuator controller 110, which controlsarray block actuator(s) 106. Computer 108 has a computer-human interfacewith a display monitor and input devices for allowing a user to operatemolecular manipulation system 100; a user may also invoke specialsoftware applications that execute on computer 108 to automate the usageof molecular manipulation system 100. The present invention may beimplemented using different types of actuators, servo motors, orpiezoelectric controllers that allow management of the movement at anatomic scale, possibly with laser-assisted guidance. For example, a typeof servo controller is disclosed in Mamin et al., “Atomic forcemicroscopy data storage system with tracking servo from lateralforce-sensing cantilever”, U.S. Pat. No. 5,856,967, issued Jan. 05,1999, herein incorporated by reference in its entirety for all purposes.

In addition to moving the proximal probes by moving the proximal probearray blocks in which the proximal probes are assembled, the proximalprobes may be implemented to include cantilevers, as explained in moredetail hereinbelow. If so included, each cantilever associated with aproximal probe is controlled through cantilever controller 112, whichmay be commanded by computer 108.

The programmable molecular manipulation system of the present inventionemploys electrostatic force via proximal probes for the manipulation ofmolecules. Electrostatic controller 114, which may also be commanded bycomputer 108, controls the amount of voltage (possibly in addition toother physical variables, such as electric current) that is experiencedby each proximal probe, thereby controlling the electrostatic force thatis presented by the tip of each proximal probe, as explained in moredetail hereinbelow. In addition, computer 108 may work with othercontroller elements. Electrostatic controller 114 or some othercontroller may also provide for magnetic manipulation of molecules,either for assistance in manipulating a molecule primarily throughelectrostatic forces or for direct manipulation of a molecule; forexample, a proximal probe may comprise a small loop of conductingmaterial that carries an electric current to present a small magneticfield toward a molecule.

With reference now to FIG. 2, a diagram depicts a proximal probe with aconductive microtip for use in an implementation of the molecularmanipulation system of the present invention. As noted above, theproximal probes of the present invention may be implemented in a varietyof forms. FIG. 2 depicts a tip of a proximal probe that does not includea cantilever, whereas FIG. 4 depicts a tip of a proximal probe that doesinclude a cantilever; in each case, the tip of the proximal probe refersto the portion of the proximal probe that expresses an electrostaticcharge that in order to impart an electrostatic force on a molecule.However, the description of the figures hereinbelow may simply describethe proximal probe expressing an electrostatic charge without referenceto the tip at the end of the proximal probe. Referring to FIG. 2, tip200 comprises conductive wire/lead 202 that forms an atomically sharpmicrotip; conductive lead 202 is centered within insulating material orsemiconductor material 204. In FIG. 2, tip 200 has been truncated forpurposes of illustration; FIG. 2 shows either a side view of tip 200 ora center-cut view of tip 200.

With reference now to FIG. 3, a diagram depicts a manner for forming aglass-insulating proximal probe with a conducting microtip for use in animplementation of the molecular manipulation system of the presentinvention. Glass rod 300 contains conductive lead/wire 302 that iscentered within glass rod 300. Glass rod 300 has been heated in region304 to make it soft and pliable, and it has been stretched to elongateregion 304, thereby making glass rod 300 and its conductive lead/wire302 much thinner in region 304. Glass rod 300 can be cut within region304 such that a microtip is formed in which only a microscopic portionof conductive wire 302 is exposed, e.g., similar to that shown in FIG.2. The process that is described with respect to FIG. 3 may be performedon multiple glass rods simultaneously such that an assembly of multipleproximal probes are manufactured more efficiently; in other words, aproximal probe array block can be manufactured in a single operation asdescribed above.

With reference now to FIG. 4, a diagram depicts a proximal probe with acantilever having a conductive microtip for use in an implementation ofthe molecular manipulation system of the present invention. Tip 400comprises conductive lead 402 that forms an atomically sharp microtip atthe end of cantilever 404; conductive wire/lead 402 is contained withinthe insulating material or the semiconductor material of cantilever 404.In FIG. 4, tip 400 has been truncated for purposes of illustration; FIG.4 shows either a side view of tip 400 or a center-cut view of tip 400.Cantilever base 406 contains structure for moving cantilever 404, whichmay be implemented in a variety of different manners. Information forcantilevers on electrostatic proximal probes is disclosed in Itoh etal., “Electrostatic force detector with cantilever for an electrostaticforce microscope”, U.S. Pat. No. 6,507,197, issued Jan. 14, 2003, hereinincorporated by reference in its entirety for all purposes; furtherdetail concerning structures of cantilevers for proximal probes isdisclosed in U.S. Pat. No. 5,856,967, referenced above.

With reference to FIG. 5, a block diagram depicts a group of proximalprobes that are assembled together to form a proximal probe array blockin accordance with an embodiment of the present invention. FIG. 5further illustrates the manner in which proximal probes that aredepicted in FIG. 2 and FIG. 4 can be grouped together to form a proximalprobe array block as depicted in FIG. 1. Proximal probes 502 areassembled to form proximal probe array block 504. It should be noted,however, that a proximal probe array block is not necessarily made fromthe gathering of individual proximal probes. Moreover, a proximal probearray block may be manufactured using lithography, gas deposition, laserablation, or some other technique.

Conductive wires/leads from each proximal probe are connected tosupporting circuitry; FIG. 5 depicts supporting circuitry 506 withinproximal probe array block 504, but the supporting circuitry may belocated outside of the proximal probe array block such that onlyconductive connections are located within the proximal probe arrayblock. Conductive wires/leads may include wires for placing, i.e.asserting or inducing, an electrostatic potential at the tip of aproximal probe, wires for controlling a cantilever of a proximal probe,wires for sensors, wires for manipulative control of a structure ofproximal probe, wires for manipulative control of a portion of asubstrate of a proximal probe array block, and/or wires for otherpurposes. Supporting circuitry 506 would be connected as necessary tohigher-level controllers, such as those shown in FIG. 1. Proximal probes502 are juxtaposed, which may mean that they contact each other or thatthey have spaces between them because they are embedded within, attachedto, or otherwise held by a layer, a block, or a substrate of material,which may consist of various types of material; in either case, it maybe assumed that the conductive wires in each proximal probe areelectrically insulated from the conductive wires in other proximalprobes, whether or not the proximal probes contact each other.

Proximal probe array block 504 may be manufactured so that proximalprobes 502 and/or the spacing between proximal probes 502 are located asnecessary for the geometry of the molecules that are to be manipulatedusing proximal probe array block 504. In addition, the figures depictthe proximal probes as having equal length or height, but the proximalprobes in any proximal probe array block may have unequal length orheight as appropriate to suit the geometry of a targeted molecule.

The figures also depict the substrate of the proximal probe array blockas being planar, but the proximal probe array blocks may have non-planarsurfaces such that the proximal probe array blocks have substantiallyconcave, convex, or more complicated shapes. The substrate of theproximal probe array block may also contain structures that may becontrolled to increase or decrease the spacing between a subset ofproximal probes in the proximal probe array block or to increase ordecrease the length or height of a subset of proximal probes from thesubstrate of the proximal probe array block, as explained andillustrated further below. The substrate of the proximal probe arrayblock is not necessarily made of a single material, and the substratemay comprise different portions that are made of different materials.

With reference now to FIG. 6, a diagram depicts a one-dimensionalproximal probe array that is presenting an electrostatic pattern whichis facing the electron cloud of a captured molecule within animplementation of the molecular manipulation system of the presentinvention. As mentioned above, the programmable molecular manipulationsystem of the present invention employs electrostatic force via proximalprobes to achieve the manipulation of molecules. However, before amolecule may be manipulated, the molecule is attracted to the proximalprobe array and then captured by the proximal probe array; the basis forthe attraction of a molecule to a proximal probe array prior tomanipulation of the molecule by the proximal probe array is describedwith respect to the illustration in FIG. 6.

Proximal probe array block 602 comprises a set of proximal probes. Atsome point in time, some of the proximal probes are purposefullyelectrostatically charged, e.g., using the components that are shown inFIG. 1. By applying, asserting, or inducing a voltage to the conductivematerial on the tip of a proximal probe, e.g., using supportingcircuitry 506 that is shown in FIG. 5 and that is ultimately controlledby an apparatus such as computer 108 that is shown in FIG. 1, anelectrostatic charge is induced or expressed, i.e. manifested or exposedto external entities. The polarity of the electric potential that isasserted on each proximal probe determines the polarity of theelectrostatic charge that is exposed by each proximal probe; someproximal probes remain neutral because no electrical voltage is appliedto those proximal probes. Thus, electrostatic pattern 604 is presentedby the set of proximal probes when the electrical potentials are appliedto the set of proximal probes.

Proximal probe array block 602 is exposed in some manner to one or moretargeted molecules. For example, proximal probe array block 602 may beinserted into a reaction container, which may be a simple container thatholds a low-temperature, low-pressure gas. Alternatively, the containerholds the targeted molecules in liquid form, or the targeted moleculesare suspended within a liquid solution, preferably using a solvent thatexhibits a lower dipole moment than water; the use of an electrostaticforce microscope within a liquid solution is described within Gemma etal., “Apparatus for estimating charged and polarized states offunctional groups in a solution”, U.S. Pat. No. 5,329,236, issued Jul.12, 1994, hereby incorporated by reference in its entirety for allpurposes. In another alternative, the targeted molecules rest as a filmor layer on a substrate, which may be a surface of a container; the useof an interfacial force microscope with respect to films is disclosed inHouston et al., “The Interfacial-Force Microscope,” Nature, vol. 356,pp. 266–267, Mar. 19, 1992, hereby incorporated by reference in itsentirety for all purposes. Preferably, a substrate that supports a filmof targeted molecules would exhibit a relatively small attractive forcewith respect to the targeted molecules such that the proximal probearray can capture a targeted molecule without employing a significantforce for overcoming the attractive force of the substrate.

The use of a proximal probe array may be separated into temporalperiods: first, a capturing phase or mode of operation in which atargeted molecule is captured by the proximal probe array; second, amanipulation phase in which a targeted molecule is manipulated by theproximal probe array; and third, a release phase in which a molecule ormolecules that are attached to the proximal probe array are releasedfrom the proximal probe array.

The goal of the capturing phase is to attract a targeted molecule to theproximal probe array by electrostatic force. In general, assuming that atarget molecule has the proper orientation, a targeted molecule within acontainer would be attracted to the electrostatic pattern that isexpressed by a proximal probe array because certain locations of atargeted molecule would have opposite polarity to the electrostaticcharge that is expressed by the proximal probe array, as explainedhereinbelow; in other words, a targeted molecule would be attracted tothe electrostatic pattern of a proximal probe array for the followingreasons.

Atoms of different elements have different abilities to attractelectrons; when atoms participate in a chemical bond, the atoms exhibitelectronegativity, i.e. an attraction for electrons in chemical bond. Ifthe electronegativities of two atoms in a chemical bond are different,an electron will spend more time around the atom that is moreelectronegative than around the other atom, thereby causing one atom ina chemical bond to appear to acquire a slight negative charge and theother atom to appear to acquire a slight positive charge. Thisseparation of charge constitutes a dipole, and many molecules exhibitmany regions or locations around their electron cloud that havedifferent degrees of polarization. A very polar molecule would bestrongly attracted to the electrostatic pattern that is presented by anelectrostatically charged proximal probe array, while a non-polarmolecule would not be attracted.

Referring again to FIG. 6, a molecule within the reaction container hasmolecular electron cloud 606, which inherently possesses locations thatexhibit polarization such that the molecule presents electrostaticpattern 608. At some point in time, the molecule would be attracted toproximal probe array block 602 such that the respective electrostaticpatterns align. A molecule that exhibits a matching pattern of points orlocations that have opposite polarity to the pattern of electrostaticcharges that are presented by a proximal probe array is said to have acomplementary electrostatic pattern to the proximal probe array'selectrostatic pattern. The electrostatic pattern that is presented bythe proximal probe array at the current point in time is termed the“current electrostatic pattern”. A molecule that has a complementaryelectrostatic pattern to the current electrostatic pattern is termed a“targeted molecule”. A targeted molecule is termed a “captured molecule”when the electrostatic pattern of the proximal probe array aligns withthe complementary electrostatic pattern of the targeted molecule; acaptured molecule may experience an attractive force such that theelectrostatic forces between the aligned points may cause the targetedmolecule to be held by the proximal probe array for a brief period oftime.

A targeted molecule may have numerous polarized locations around itselectron cloud. It should be noted that the electrostatic pattern on aproximal probe array may be used such that each proximal probe isintended to be directed at a single, unique, polarized location on atargeted molecule; this is the preferred, default case in which there isa one-to-one relationship between proximal probes and a targetedmolecule's polarized locations. However, the electrostatic pattern on aproximal probe array may be used such that a single, unique, proximalprobe is intended to be directed at multiple, unique, polarizedlocations on a targeted molecule, e.g., by using a stronger electricpotential on a proximal probe such that it influences multiple polarizedlocations, because the polarized locations are relatively close comparedto the size of the proximal probe. Moreover, the electrostatic patternon a proximal probe array may be used such that multiple proximal probesare intended to be directed at a single, unique, polarized location on atargeted molecule, e.g., given the geometry of the targeted molecule,the degree of polarity of the polarized location, and the geometry ofthe proximal probe array. Each of the above-noted cases may be employedsimultaneously within a single electrostatic pattern on the proximalprobe array.

Given the fact that a targeted molecule may have numerous polarizedlocations, it should also be noted that the electrostatic pattern on aproximal probe array may target only a subset of the polarized locationson a targeted molecule. In some cases, a subset of the targetedmolecule's polarized locations may be deemed sufficient to capture atargeted molecule; in other cases, the geometry of a targeted moleculemay prohibit the practical attraction of some of the polarized locationsof the targeted molecule. Hereinbelow, each of the polarized locationsfrom the set of polarized locations on a targeted molecule that aredesignated to be points of attraction by the electrostatic pattern on aproximal probe array are termed “capture points” of the targetedmolecule.

With reference now to FIG. 7, a diagram depicts a frontal, edge-on viewof a one-dimensional proximal probe array block within an implementationof the molecular manipulation system of the present invention. In thisillustration, the tips of the proximal probes in the proximal probearray block are not shown; instead, each proximal probe is representedby the electrostatic charge that is asserted on the respective tip ofeach proximal probe. In this manner, the proximal probe array is said topresent an electrostatic charge pattern, e.g. electrostatic pattern 702,that corresponds to the asserted electric potentials.

With reference now to FIG. 8, a diagram depicts a two-dimensionalproximal probe array that can present an electrostatic pattern forattempting to capture a targeted molecule that exhibits an electroncloud that contains polarized locations in accordance with an embodimentof the present invention. FIG. 8 illustrates that molecular electroncloud 802 is a three-dimensional entity that exhibits athree-dimensional arrangement of polarized locations. In contrast to theone-dimensional proximal probe array block in FIG. 6 that has proximalprobes that are arranged substantially linearly, two-dimensionalproximal probe array block 804 contains proximal probes that arearranged over an area, thereby partially addressing the challenge ofcapturing a molecule, all of which are three-dimensional entities withcomplex electron clouds. In a preferred embodiment, the proximal probesare equally-spaced over the area with uniformly-sized gaps between theproximal probes, but a proximal probe array block may be manufacturedsuch that the proximal probes are arranged over an area in a variety oflocations with varying gap sizes to suit the geometry of a targetedmolecule, possibly in addition to a complex shape for the substrate ofthe proximal probe array block. In the exemplary embodiment of thepresent invention that is illustrated within FIG. 8, sensors such assensor probe 806, are interspersed among the proximal probes in proximalprobe array block 804; these sensors are described in more detailfurther below. It should be noted that sensor probes may also beemployed within one-dimensional proximal probe array blocks; however,various embodiments of the present invention may or may not comprisesensor probes.

It should also be noted that a proximal probe may act as its owndetector; after a targeted molecule is captured, a capture point of thetargeted molecule should affect the electrical characteristics of thetip of a proximal probe. By analyzing the electric current through theconducting wire/lead of a given proximal probe or by analyzing thefluctuation of the voltage and/or current that is experienced by theconducting wire/lead, e.g., before, during, and after the capture of atargeted molecule, one may discern whether or not the tip of theproximal probe is in proximity with a captured molecule, or preferably,in proximity with a capture point of a targeted molecule after itscapture.

With reference now to FIG. 9, a diagram depicts a frontal, edge-on viewof a two-dimensional proximal probe array block within an implementationof the molecular manipulation system of the present invention. In amanner similar to that shown in FIG. 7, the tips of the proximal probesin a proximal probe array block are not shown; instead, each proximalprobe is represented by the electrostatic charge that is asserted on therespective tip of each proximal probe. In contrast to FIG. 7, whichshows a one-dimensional proximal probe array block, FIG. 9 depicts atwo-dimensional proximal probe array block that presents electrostaticpattern 902.

In the exemplary embodiment that is shown in FIG. 9, the uniformarrangement of proximal probes within a two-dimensional proximal probearray block is reflected by the uniform arrangement of the electrostaticpattern that is represented within FIG. 9. In the example that is shownin FIG. 9, each row of the two-dimensional proximal probe array may beregarded as a one-dimensional proximal probe array; the two-dimensionalproximal probe array in FIG. 9 comprises rows 904, 906, 908, and 910. Inthis example, a set of one-dimensional proximal probe arrays alignedalong a different axis than the axis of the one-dimensional proximalprobe arrays comprises a two-dimensional proximal probe array; forexample, a two-dimensional proximal probe array may be formed bystacking a set of one-dimensional proximal probe arrays.

However, each of the one-dimensional proximal probe arrays in atwo-dimensional proximal probe array does not necessarily share the samegeometry; for example, different proximal probe arrays may havedifferent inter-probe gaps or spacings. Moreover, as noted hereinabove,proximal probes may be arranged over an area in a variety of locationswith varying gap sizes to suit the geometry of a targeted molecule, anda two-dimensional proximal probe array may have a different geometry. Inthese alternative embodiments, the non-uniform arrangement of proximalprobes within a two-dimensional proximal probe array block might bereflected by a non-uniform arrangement of an electrostatic pattern,which is not shown in FIG. 9.

With reference now to FIG. 10, a diagram depicts a single row of atwo-dimensional proximal probe array that is presenting an electrostaticpattern which is facing the electron cloud of a captured molecule withinan implementation of the molecular manipulation system of the presentinvention. FIG. 10 is similar to FIG. 6, but FIG. 10 differs from FIG. 6in that the depicted one-dimensional proximal probe array block ismerely one row of a set of one-dimensional proximal probe array blocksthat collectively comprise a two-dimensional proximal probe array block;in other words, FIG. 10 illustrates a horizontal, cut-away slice or viewof a single row 1002 of a two-dimensional proximal probe array block,such as that shown in FIG. 8. More specifically, single row 1002 of atwo-dimensional proximal probe array corresponds to row 906 that isshown in FIG. 9. Molecular electron cloud 1004 represents a horizontal,cut-away slice or view of a three-dimensional molecular electron cloud,such as molecular electron cloud 806 that is shown in FIG. 8.

With reference to FIG. 11, a diagram depicts a pair of juxtaposedtwo-dimensional proximal probe array blocks that can be used to capturea targeted molecule in accordance with an embodiment of the presentinvention. The description of FIG. 1 mentions that multiple proximalprobe array blocks may be employed within a single programmablemolecular manipulation system. FIG. 11 and FIG. 12 depict two differentconfigurations for using multiple proximal probe array blocks; FIG. 11illustrates juxtaposed proximal probe array blocks, whereas FIG. 12illustrates opposing or facing proximal probe array blocks. In eithercase, the molecular manipulation system can be described as having athree-dimensional arrangement of proximal probes; larger, more complex,three-dimensional configurations of proximal probes can be achievedusing more numerous proximal probe array blocks. It should also benoted, though, that a molecular manipulation system may comprise one ormore individual proximal probes that are configured to be used with atleast one proximal probe array block; the individual proximal probes mayalso be manipulated individually in an opposing or juxtaposed positionwith respect to a proximal probe array block.

FIG. 11 depicts a pair of juxtaposed two-dimensional proximal probearray blocks 1102 and 1104 that are separated by inter-block gap 1106.The size of inter-block gap 1106 may vary and may be adjustable by anoperator, e.g., using the controlling mechanisms that are shown in FIG.1; in particular, each of proximal probe array blocks 1102 and 1104 maybe uniquely associated with an actuator mechanism such that proximalprobe array blocks 1102 and 1104 can be moved independently of the otherproximal probe array block. A single electrostatic pattern may be sharedby each proximal probe array, or two electrostatic patterns may be usedsuch that each proximal probe array may present unique electrostaticpatterns. Proximal probe array blocks 1102 and 1104 may be operated tocapture a single targeted molecule, to capture two unique targetedmolecules, or to capture two identical targeted molecules.

With reference to FIG. 12, a diagram depicts a pair of opposingtwo-dimensional proximal probe array blocks that can be used to capturea targeted molecule in accordance with an embodiment of the presentinvention. FIG. 12 depicts one row from each of a pair of opposingtwo-dimensional proximal probe array blocks 1202 and 1204 that areseparated by inter-block gap 1206; it may be assumed that FIG. 12illustrates a top view or a horizontal, cut-away view or slice of twocomplete, two-dimensional, proximal probe array blocks in the mannerthat is shown in FIG. 10. The size of inter-block gap 1206 may vary andmay be adjustable by an operator, e.g., using the controlling mechanismsthat are shown in FIG. 1; in particular, each of proximal probe arrayblocks 1202 and 1204 may be uniquely associated with an actuatormechanism such that proximal probe array blocks 1202 and 1204 can bemoved independent of the other proximal probe array block. A singleelectrostatic pattern may be shared by each proximal probe array, or twoelectrostatic patterns may be used such that each proximal probe arraymay present unique electrostatic patterns. Proximal probe array blocks1202 and 1204 may be operated to capture a single targeted molecule, tocapture two unique targeted molecules, or to capture two identicaltargeted molecules. In the example that is shown in FIG. 12, a singlecaptured molecule is represented by a top view or a horizontal, cut-awayview or slice of molecular electron cloud 1208.

With reference now to FIG. 13, a flowchart depicts a process for usingproximal probe arrays to manipulate molecules in accordance with anembodiment of the present invention. The description of the previousfigures merely mentioned that molecules may be manipulated, but thefocus of the majority of the description of the figures has beendirected to explaining the manner in which a proximal probe array may beused to capture a targeted molecule or molecules. The process that isillustrated within FIG. 13 provides a foundation for describing thedifferent types of molecular manipulation that may be performed, whichare described in more detail hereinbelow.

The process commences with the selection of an electrostatic pattern forone or more proximal probe arrays (step 1302). The selection may beperformed in accordance with input from a user of the molecularmanipulation system, or the selection may be automatically andprogrammatically performed, preferably in accordance with configurationparameters that guide the operation of the manipulation procedure,wherein one or more of the configuration parameters may have beenselected by a user.

The proximal probe array is then energized in accordance with theselected electrostatic pattern (step 1304) by asserting or not assertingan electrical potential on each proximal probe in the proximal probearray as is indicated by a position in the electrostatic pattern thatcorresponds to each proximal probe. The electrostatic patterns may behardwired in the molecular manipulation system, or the electrostaticpatterns may be managed in software by storing the electrostaticpatterns as data in one or more data structures or memories. Forexample, a database of electrostatic patterns may be accessible tocomputer 108 that is shown in FIG. 1.

In a simple case, each proximal probe may be represented by a data flagwithin a data structure that represents the electrostatic pattern; theposition of a data flag within the data structure corresponds to theposition of a proximal probe in a proximal probe array in a one-to-onerelationship. The data flags may be implemented using two binary bitsthat allow four values: a first value represents that a positiveelectric potential should be applied to the corresponding proximalprobe; a second value represents that a negative electric potentialshould be applied to the corresponding proximal probe; a third valuerepresents that the corresponding proximal probe should have noelectrical potential, i.e. tied to ground; and a fourth value mightrepresent a don't care value in which the electrical potential that isapplied to the proximal probe may have either a positive or a negativeelectric potential. The data flags would be mapped when necessary tovoltages that are to be applied to corresponding proximal probes, e.g.,using electrostatic controller 114 that is shown in FIG. 1.

Alternatively, each proximal probe may be represented by a record withinone or more database files that are stored within one or more memories.Each database file may represent an electrostatic pattern, wherein eachrecord contains multiple fields for various parameters that are used toindividually control a variety of physical characteristics or physicalvariables that are associated with each proximal probe. For example, itmay be advantageous to apply different voltages on different proximalprobes in accordance with different capture points that are targeted bydifferent proximal probes, and the values for the voltages would bestored as merely one of the parameters within the corresponding record.The position of a record within this type of database file maycorrespond with the position of a proximal probe in a proximal probearray in a one-to-one relationship; alternatively, the record maycontain identifying coordinates for indicating the relative position ofthe proximal probe to which the record corresponds. The records would bemapped when necessary to voltages and/or other types of physicalvariables that are to be applied to corresponding proximal probes, e.g.,via electrostatic controller 114 that is shown in FIG. 1.

After energizing the proximal probe array, the proximal probe arrayblock is presented to targeted molecules within a reaction container: avolume of low-temperature, low-pressure gas that contains the targetedmolecules in a gaseous state; a volume of liquid in a reaction chamberor container that contains the targeted molecules in a liquid state; ora film or layer that contains the targeted molecules, wherein the filmor layer has been deposited on a surface or substrate. A set of one ormore proximal probes would present an electrostatic charge pattern tothe targeted molecules, and the electrostatic charge would attractpolarized locations or capture points on the targeted molecules.

At some point in time, a molecule would be captured by the proximalprobe array (step 1306), and an optional check may be made to ensurethat the captured molecule is the targeted molecule that the operatordesired to manipulate (step 1308). The capture of a molecule may beoptionally detected using sensing detectors that are incorporated intothe proximal probe array and/or are connected to the proximal probearray; in addition, the captured molecule may be optionally verified asbeing an instance of the targeted molecule rather than a random moleculethat happens to be captured by the proximal probe array. Referring againto FIG. 8, proximal probe array block 802 depicts sensors interspersedamongst the proximal probes. A sensor does not necessarily have the sameform or structure as a proximal probe, and a variety of sensor types maybe incorporated into the proximal probe array block; for example, U.S.Pat. No. 6,507,197, incorporated above, discloses the use ofelectrostatic force detectors in conjunction with an electrostatic forcemicroscope. Other techniques may be used to detect the capture of atargeted molecule, such as using spectrographic techniques on thereflected light from a laser beam that is aimed at the capturedmolecule. In addition, as noted above, a proximal probe may act as itsown detector.

Referring again to FIG. 13, if a targeted molecule has been captured,then a programmed procedure or manual operation is performed tomanipulate the captured molecule (step 1310), possibly using multipleproximal probe array blocks and/or multiple captured molecules. Afterthe manipulation is performed, or if the captured molecule was not thetargeted molecule at step 1308, then the proximal probe array block isde-energized to release the captured molecule or molecules (step 1312),e.g., by canceling the applied voltages to the proximal probes that werepreviously charged/energized; the manipulated molecule may optionally beheld by the proximal probe array block by omitting step 1312 if asubsequent molecular manipulation is desired, as explained in moredetail further below. A determination is made as to whether or notanother manipulation procedure is to be performed (step 1314), and ifso, then the process branches back to step 1302 to capture andmanipulate another molecule; if not, then the process is concluded.

With reference now to FIG. 14, a diagram depicts a proximal probe arrayblock that is attempting to capture and hold one of a set of targetedmolecules that are deposited as a film on a surface. Surface/substrate1402 supports a film of targeted molecules that are represented by theirmolecular electron clouds 1404–1410. Proximal probe array block 1412 ismoved into a position over the film of targeted molecules to try tocapture the targeted molecule that is represented by molecular electroncloud 1408. When the gap between proximal probe array block 1412 and thetargeted molecule is below a certain value, the targeted molecule wouldbe attracted to the proximal probe array block by an electrostatic forcethat is greater than the attractive forces between the targeted moleculeand other molecules within the film and that is greater than the forceof gravity that acts to pull the targeted molecule toward the surfacebelow it. The targeted molecule could then be described as beingcaptured by the proximal probe array block, which would hold thecaptured molecule until it is released by the proximal probe array oruntil the captured molecule has experienced an event that might causethe release of the captured molecule, such as a collision with arelatively high-energy molecule in a gaseous state that acts to knockthe captured molecule from the proximal probe array.

The previously described figures illustrate various examples ofstructures that may be used to capture and manipulate a molecule inaccordance with an embodiment of the present invention. FIG. 13illustrates a process for using those structures to manipulate amolecule; step 1310 is directed to the process step by which aprogrammed procedure or manual operation is performed to manipulate thecaptured molecule. However, the previously described figures have notillustrated the details of the various ways that a molecule may bemanipulated in accordance with the molecular manipulation system of thepresent invention, which is described in more detail hereinbelow withrespect to the remaining figures. It should be noted that the term“manipulation” may refer to many different types of actions thatinclude, but is not limited to, stretching, stressing, shearing,modifying, bending, twisting, combining, binding, fusing, uniting,ripping, breaking, rendering, or any other actions that are related tophysical transformation, possibly on one molecule but possibly on two ormore molecules.

With reference now to FIGS. 15A–15C, a set of diagrams depict a methodof using a proximal probe array to shift an electrostatic pattern over ashort period of time in accordance with an embodiment of the presentinvention. As discussed above, a captured molecule on a proximal probearray is held in place by maintaining the electrostatic forces that aregenerated by an electrostatic pattern on the proximal probe array. Asone of the techniques for manipulating a captured molecule using aproximal probe array, those same electrostatic forces that are used tohold a captured molecule are also used to move the captured molecule bymodifying the electrostatic pattern.

Electrostatic pattern 1502 is similar to electrostatic pattern 702 thatis shown in FIG. 7. Over a relatively short period of time,electrostatic pattern 1502 can be modified to electrostatic pattern1504; the duration of the modification time period may be a configurableparameter, e.g., via a software application that is executing oncomputer 108 as shown in FIG. 1.

The modification of the electrostatic pattern may occur in a variety ofways; it should be not assumed that the examples that are providedherein comprise an exhaustive list. In one exemplary embodiment, theelectrostatic pattern is shifted during the modification time period ina manner similar to a bit shift in a computer memory, wherein thecomplete shift operation occurs over a series of shorter time periodsusing a series of smaller shift operations, preferably individual bitshifts, as shown in FIG. 15B. During one of the shorter time periods,each proximal probe in a first subset of the proximal probes, which mayor may not be in an energized state, i.e. may or may not be exhibitingan electrostatic charge, accepts the state of the adjacent proximalprobe; meanwhile, a second subset of proximal probes, which may or maynot be in an energized state, accept the state of the adjacent proximalprobe. The shorter shift operation is then repeated as many times asnecessary to complete the overall shift operation that results in themodification of the electrostatic pattern.

Another way to modify the electrostatic pattern is similar to the seriesof smaller, adjacent shifts as described above, but in this alternativeexample, the smaller shift operations are regarded as being more likeanalog operations rather than like discrete, digital operations. In thissecond example, the states of the proximal probes are changed spatiallyin a manner similar to that described above; the states of a first setof proximal probes are modified while also modifying the states of asecond set of proximal probes, wherein each of proximal probes in thesecond set of proximal probes is adjacent to a proximal probe in thefirst set of proximal probes. Alternatively, the states of the proximalprobes are not necessarily adjacent but are relatively close, whereinthe distance is also configurable.

However, in this second example, the states of the proximal probes areshifted temporally in a different manner. In this second example, thestates of the proximal probes are shifted gradually in accordance with afunction rather than abruptly in a discrete manner, e.g., as illustratedby function 1506 in FIG. 15C; the function may be a configurableparameter that is selected manually by an operator or programmaticallyby the molecular manipulation system, and the parameters for thefunction may also be configurable. Hence, during one of the smaller timeperiods, the electric potentials on some of the proximal probes aregradually decreased while the electric potentials on other proximalprobes are gradually increased. For example, function 1506 in FIG. 15Cmay represent the voltage on a first proximal probe, and function 1508in FIG. 15D may represent the voltage on a second proximal probe that isadjacent to the first proximal probe. FIG. 15C and FIG. 15D representthe same time period; as the voltage is being decreased on the firstproximal probe, the voltage is being increased on the second proximalprobe. The shorter shift operation is then repeated as many times asnecessary to complete the overall shift operation that results in themodification of the electrostatic pattern.

As noted above, there are different types of manipulation. Thesedifferent types of manipulation can be achieved by modifying theelectrostatic pattern in different ways.

With reference now to FIG. 16A, a diagram depicts a method for using aproximal probe array block to move a targeted molecule in accordancewith an embodiment of the present invention. FIG. 16A depicts an examplein which an entire electrostatic pattern on a proximal probe array blockmay be shifted, e.g., using the examples that are discussed above withrespect to FIGS. 15A–15C, in order to accomplish a move operation as oneof the types of manipulation of a molecule. When an entire electrostaticpattern is shifted, the entire pattern of electrostatic forces are alsoshifted. Given that the captured molecule has polarized locations, i.e.capture points, that are attracted by the proximal probes that areexerting an electrostatic force, the capture points remain attracted tothose proximal probes during the shifting operation, and the capturepoints also move during the shifting operation. Hence, the capturedmolecule may be moved as a whole around the proximal probe array byshifting the electrostatic pattern.

In a manner similar to that shown in FIG. 6, proximal probe array block1602 comprises a set of proximal probes, which have been energized withan electric potential so that the proximal probes exhibit electrostaticpattern 1604. A captured molecule has molecular electron cloud 1606,which possesses inherent capture points that exhibit polarization suchthat the molecule presents electrostatic pattern 1608. At some point intime, the molecule would be attracted to proximal probe array block 1602such that the respective electrostatic patterns align, and the moleculewould be captured by proximal probe array block 1602, e.g., as describedwith respect to FIG. 14.

At some subsequent point in time, portions of the electrostatic patternon proximal probe array block 1602 are shifted to create electrostaticpattern 1610. Capture points that are represented by electrostaticpattern 1608 in molecular electron cloud 1606 follow electrostaticpattern 1610 such that the captured molecule is also shifted when theelectrostatic pattern on proximal probe array block is shifted.

With reference now to FIG. 16B, a diagram depicts a method for using aproximal probe array block to bend or flex a targeted molecule inaccordance with an embodiment of the present invention. FIG. 16B depictsan example in which a portion of an electrostatic pattern on a proximalprobe array block may be shifted in order to accomplish a bending orflex operation as one of the types of manipulation of a molecule. Whenonly a portion of the whole electrostatic pattern is shifted, then onlya portion of the electrostatic forces are also shifted. The capturepoints of the captured molecule remain attracted to their respectiveproximal probes during the shifting operation; a portion of the capturepoints move during the shifting operation while the remainder of thecapture points remain attracted to a fixed location. Hence, the capturedmolecule bends or flexes with the partial shifting of the electrostaticpattern.

FIG. 16B is similar to FIG. 16A; identical reference numerals refer toidentical elements. Proximal probe array block 1602 exhibitselectrostatic pattern 1604, which has captured a molecule that hasmolecular electron cloud 1606 that contains the capture points that arerepresented by electrostatic pattern 1608.

At some subsequent point in time, portions of the electrostatic patternon proximal probe array block 1602 are shifted to create electrostaticpattern 1612. Capture points that are represented by electrostaticpattern 1614 in molecular electron cloud 1606 follow electrostaticpattern 1612 such that the captured molecule is stretched or elongatedwhen the electrostatic pattern on proximal probe array block is shifted.The degree to which a captured molecule may be bent or flexed woulddepend somewhat on the type of molecule.

With reference now to FIG. 16C, a diagram depicts a method for using aproximal probe array block to twist or pivot a portion of a targetedmolecule in accordance with an embodiment of the present invention. FIG.16C depicts an example in which a portion of an electrostatic pattern ona proximal probe array block is shifted and pivoted around a point inorder to accomplish a twisting or torque operation as one of the typesof manipulation. When only a portion of the whole electrostatic patternis shifted, then only a portion of the electrostatic forces are alsoshifted, and the captured molecule bends or flexes with the partialshifting of the electrostatic pattern, as described above. However,instead of shifting the electrostatic pattern in a simple linearfashion, the electrostatic pattern may be rotated about an axis. Again,the capture points of the captured molecule remain attracted to theirrespective proximal probes during the shifting operation, and a portionof the capture points rotate during the shifting operation while theremainder of the capture points remain attracted to a fixed location.Hence, the captured molecule twists with the partial shifting of theelectrostatic pattern.

FIG. 16C is similar to FIG. 9; each depicts a two-dimensionalelectrostatic pattern on a proximal probe array block. The electrostaticpattern in FIG. 16C consists of portion 1616 and portion 1618. At somesubsequent point in time, portion 1616 of the electrostatic pattern isrotated ninety degrees clockwise to form portion 1620 of theelectrostatic pattern while portion 1618 remains unmodified. Assumingthat the electrostatic pattern had previously captured a molecule, asubset of the capture points on the captured molecule would followelectrostatic pattern 1616 as it is shifted such that a portion of thecaptured molecule is twisted when the electrostatic pattern on proximalprobe array block is shifted.

Alternatively, the electrostatic pattern may have previously capturedtwo molecules: a first molecule may be held by portion 1616 of theelectrostatic pattern while a second molecule may be held by portion1618 of the electrostatic pattern. At some subsequent point in time,shifting portion 1616 of the electrostatic pattern to form portion 1620of the electrostatic pattern would rotate the first molecule; sinceportion 1618 remains unshifted, the second molecule would remainunmoved.

With reference now to FIG. 16D, a diagram depicts a method for using aproximal probe array block to break a targeted molecule in accordancewith an embodiment of the present invention. FIG. 16D depicts an examplein which a first portion of the electrostatic pattern may be shiftedwhile a second portion of the electrostatic pattern is shifted in anopposite or different direction; this operation is similar to theoperation that is illustrated in FIG. 15A or FIG. 15B. Again, thecapture points of the captured molecule remain attracted to theirrespective proximal probes during the shifting operation. A first subsetof the capture points are shifted along with the first portion of theelectrostatic pattern while a second subset of the proximal probes areshifted along with the second portion of the electrostatic pattern.Hence, the captured molecule bends or flexes with the shifting portionsof the electrostatic pattern, and if the stress on a chemical bondbetween atoms within the molecule is large enough, the chemical bondwill break.

FIG. 16D is similar to FIG. 16A; identical reference numerals refer toidentical elements. Proximal probe array block 1602 comprises a set ofproximal probes, which have been energized with an electric potential sothat the proximal probes exhibit electrostatic pattern 1604. A capturedmolecule has molecular electron cloud 1606, which possesses inherentcapture points that exhibit polarization such that the molecule presentselectrostatic pattern 1608. At some point in time, the molecule would beattracted to proximal probe array block 1602 such that the respectiveelectrostatic patterns align, and the molecule would be captured byproximal probe array block 1602.

At some subsequent point in time, portions of the electrostatic patternon proximal probe array block 1602 are shifted to create electrostaticpattern 1622, and the captured molecule bends or flexes with theshifting portions of the electrostatic pattern. If the stress on achemical bond between atoms within the molecule is large enough, thenthe chemical bond will break, thereby splitting or breaking the capturedmolecule into two different molecules, which are represented bymolecular electron cloud 1624 and molecular electron cloud 1626. Theproximal probe array can then be de-energized by terminating thevoltages on the appropriate proximal probes, and the captured moleculeswould be released.

It should be noted that the polarization locations on the splitmolecules may differ from the polarization locations on the originalmolecule because the split molecules may have very different structuresfrom the constituent pieces of the original molecule, thereby generatingdifferent dipole moments. Thus, it is possible that electrostaticpattern 1622 would repel molecular electron cloud 1624 and molecularelectron cloud 1626 immediately after the split operation.

The manner in which electrostatic pattern 1604 is divided into separateportions for the shifting operation can be controlled as a configurationparameter, thereby allowing the molecular manipulation system to targeta specific chemical bond within the captured molecule. Given that thestress on a chemical bond increases as the captured molecule is bent orflexed over a greater distance, it should be noted that a similar resultmight be obtained by shifting only one portion of the electrostaticpattern albeit a greater distance.

With reference now to FIG. 17, a diagram depicts a method for using aproximal probe array to create a molecule by combining two targetedmolecules in accordance with an embodiment of the present invention.Whereas FIG. 16D illustrates a splitting operation, FIG. 17 illustratesa combining operation; thus, FIG. 17 is similar to FIG. 16D except thatthe temporal aspects are reversed.

Proximal probe array block 1702 comprises a set of proximal probes,which have been energized with an electric potential so that theproximal probes exhibit electrostatic pattern 1704. Two unique, capturedmolecules are represented by molecular electron cloud 1706 and molecularelectron cloud 1708. The captured molecules may be different; however,the captured molecules may be identical because, even though molecularelectron cloud 1706 and molecular electron cloud 1708 are illustrateddifferently, the entire electron cloud might not be illustrated.

At some subsequent point in time, portions of the electrostatic patternon proximal probe array block 1704 are shifted to create electrostaticpattern 1710, and the captured molecules are brought into closeproximity when the captured molecules move with the shifted portions ofthe electrostatic pattern. Assuming that the captured molecules havesome degree of chemical affinity for each other, a chemical bond is madebetween the captured molecules such that they form a single capturedmolecule, which is represented by molecular electron cloud 1712. Theproximal probe array can then be de-energized by terminating thevoltages on the appropriate proximal probes, and the captured moleculewould be released.

It should be noted that the polarization locations on the createdmolecule may differ from the polarization locations on the originalmolecules because the created molecule may have a completely differentstructure than the constituent structures of the original molecules,thereby generating completely different dipole moments in the createdmolecule. Thus, it is possible that electrostatic pattern 1710 wouldrepel molecular electron cloud 1712 immediately after the combinationoperation.

With reference now to FIG. 18, a diagram depicts a method for usingmultiple proximal probe arrays to create a molecule by combining twotargeted molecules in accordance with an embodiment of the presentinvention. Whereas FIG. 17 illustrates a combining operation using oneproximal probe array block, FIG. 18 illustrates a combining operationusing two proximal probe array blocks. Proximal probe array blocks 1802and 1804 have been energized with an electrostatic pattern. Two unique,captured molecules are represented by molecular electron cloud 1806 andmolecular electron cloud 1808.

At some subsequent point in time, portions of the electrostatic patternon proximal probe array block 1804 are modified to create a newelectrostatic pattern, e.g., by shifting the original electrostaticpattern, and the captured molecules are brought into close proximitywhen captured molecule 1808 moves with the shifted portion of theelectrostatic pattern. Assuming that the captured molecules have somedegree of chemical affinity for each other, a chemical bond is madebetween the captured molecules such that they form a single capturedmolecule, which is represented by molecular electron cloud 1810. Theproximal probe array can then be de-energized by terminating thevoltages on the appropriate proximal probes, and the captured moleculewould be released.

The molecular manipulation operations that are described with respect toFIGS. 15–18 are achieved solely through electrical means; morespecifically, the molecular manipulation operations are accomplishedonly through modification of the electrostatic pattern on a proximalprobe array. However, other molecular manipulation operations can beachieved through mechanical means; more specifically, other molecularmanipulation operations can be accomplished by movement of tips ofproximal probes and/or by movement of proximal probe array blocks, asdescribed in more detail further below with respect to the remainingfigures.

With reference now to FIG. 19, a diagram depicts a pair of cantileveredtips at the ends of proximal probes on a proximal probe array in whichthe tips are flexed to split a captured molecule in accordance with anembodiment of the present invention. Tip 1902 is the end portion of aproximal probe that is assembled with other proximal probes in aproximal probe array; tip 1904 is the end portion of an adjacentproximal probe. The proximal probe array block has already captured amolecule, which is represented by molecular electron cloud 1906. Tips1902 and 1904 are exerting an electrostatic force on the capture pointsof the captured molecule.

At a subsequent point in time, the cantilever portions of tips 1902 and1904 are controlled through electronic circuitry to flex in lateral butopposite directions. The capture points of the captured molecule remainattracted to their respective tips during the flexing operation, and thecaptured molecule bends or flexes with the flexing tips. If the stresson a chemical bond between atoms within the molecule is large enough,the chemical bond will break, which results in the formation of twomolecules from the captured molecule, which are represented by molecularelectron clouds 1908 and 1910. The tips can then be de-energized byterminating the voltages on the appropriate proximal probes, and thecaptured molecules would be released. In this manner, a variety ofmolecular manipulation operations, such as the splitting operation thatis shown in FIG. 19, can be accomplished by movement of the cantileveredtips of a set of proximal probes; the number of proximal probes that maybe used in this manner may vary with the geometry of the capturedmolecule.

With reference now to FIG. 20, a diagram depicts a pair of juxtaposedproximal probe array blocks in which the proximal probe array blocks aremoved to split a captured molecule in accordance with an embodiment ofthe present invention. As noted above, multiple proximal probe arrayblocks may be used to manipulate one or more molecules simultaneously.Proximal probe array blocks 2002 and 2004 are separated by inter-blockgap 2006 in a manner similar to that shown in FIG. 11. Proximal probearray blocks 2002 and 2004 have already captured a single molecule,which is represented by molecular electron cloud 2008.

At a subsequent point in time, proximal probe array blocks 2002 and 2004are controlled through electronic circuitry to move in lateral butopposite directions, which enlarges the inter-block gap between proximalprobe array blocks 2002 and 2004, which is shown as inter-block gap2010; alternatively, the proximal probe array blocks could be translatedand rotated in a variety of orientations. The capture points of thecaptured molecule remain attracted to their attracting proximal probesduring the moving operation, and the captured molecule stretches withthe moving proximal probes. If the stress on a chemical bond betweenatoms within the molecule is large enough, the chemical bond will break,which results in the formation of two molecules from the capturedmolecule, which are represented by molecular electron clouds 2012 and2014. The proximal probes can then be de-energized by terminating thevoltages on the appropriate proximal probes, and the captured moleculeswould be released. In this manner, a molecular manipulation operation,e.g., splitting, can be accomplished by movement of a set of proximalprobe array blocks; the number of proximal probe array blocks that maybe used in this manner may vary with the geometry of the capturedmolecule.

With reference now to FIG. 21, a diagram depicts a pair of opposingproximal probe array blocks in which the proximal probe array blocks aremoved to split a captured molecule in accordance with an embodiment ofthe present invention. In a manner similar to that shown in FIG. 20, apair of proximal probe array blocks are holding a single capturedmolecule. Proximal probe array blocks 2102 and 2104 are separated by aninter-block gap in a manner similar to that shown in FIG. 12. Proximalprobe array blocks 2102 and 2104 have already captured a singlemolecule, which is represented by molecular electron cloud 2106. WhereasFIG. 20 depicts a molecular manipulation operation that can be describedas tearing the captured molecule, FIG. 21 depicts a molecularmanipulation operation that can be described more like a shearingoperation on the captured molecule.

At a subsequent point in time, proximal probe array blocks 2102 and 2104are controlled through electronic circuitry to move in lateral butopposite directions; alternatively, the proximal probe array blockscould be translated and rotated in a variety of orientations. Thecapture points of the captured molecule remain attracted to theirattracting proximal probes during the moving operation, and the capturedmolecule stretches with the moving proximal probes. If the stress on achemical bond between atoms within the molecule is large enough, thechemical bond will break, which results in the formation of twomolecules from the captured molecule, which are represented by molecularelectron clouds 2110 and 2112. The proximal probes can then bede-energized by terminating the voltages on the appropriate proximalprobes, and the captured molecules would be released. In this manner, amolecular manipulation operation, e.g., shearing, can be accomplished bymovement of a set of proximal probe array blocks; the number of proximalprobe array blocks that may be used in this manner may vary with thegeometry of the captured molecule.

With reference now to FIG. 22, a diagram depicts a pair of opposingproximal probe array blocks in which one of the proximal probe arrayblocks is moved to flex a captured molecule in accordance with anembodiment of the present invention. In a manner similar to that shownin FIG. 21, a pair of proximal probe array blocks are holding a singlecaptured molecule. Proximal probe array blocks 2202 and 2204 areseparated by an inter-block gap in a manner similar to that shown inFIG. 12. Proximal probe array blocks 2202 and 2204 have already captureda single molecule, which is represented by molecular electron cloud2206.

At a subsequent point in time, proximal probe array block 2204 iscontrolled through electronic circuitry to be translated and rotated.The capture points of the captured molecule remain attracted to theirattracting proximal probes during the manipulation operation, and thecaptured molecule stretches with the moving proximal probes, therebyimparting a different shape to the captured molecule.

Before the proximal probes are de-energized, various other operationsmay be performed. For example, another proximal probe array blockholding a different captured molecule may be brought into closeproximity with molecular electron cloud 2206 in its flexed shape,thereby allowing a chemical reaction to occur between the two capturedmolecules that would not otherwise occur if the molecules were in closeproximity but retained their normal shapes.

While the captured molecule has its flexed shape, another operation thatmight be performed would be to quickly release the captured moleculefrom the proximal probe arrays. Given the flexed shape at its release,the captured molecule may change its structure such that its restingshape is different from the resting shape that it possessed when it waspreviously captured. The properties of the newly formed molecule couldthen be studied. For example, a protein molecule may fold into adifferent shape after its release, and the properties of the newlygenerated protein could be studied.

With reference now to FIG. 23, a diagram depicts a method for using aproximal probe array block to manipulate a targeted molecule in whichthe proximal probe array block has a self-contained modification elementin accordance with an embodiment of the present invention. FIG. 23 issimilar to FIG. 16B in the following manner. Proximal probe array block2302 exhibits electrostatic pattern 2304, which has captured a moleculethat has molecular electron cloud 2306 that contains the capture pointsthat are represented by electrostatic pattern 2308. At some subsequentpoint in time, the electrostatic pattern on proximal probe array block2302 is modified to create electrostatic pattern 2310. Capture pointsthat are represented by electrostatic pattern 2312 in molecular electroncloud 2306 follow electrostatic pattern 2310 such that the capturedmolecule is stretched or elongated when the electrostatic pattern onproximal probe array block is modified.

However, FIG. 23 differs from FIG. 16B in the following manner. WhereasFIG. 16B depicted an illustration in which the electrostatic patternthat is exhibited on a proximal probe array block is modified byshifting the pattern of the electrostatic charges that are presented bythe proximal probes, FIG. 23 illustrates an example in which thestructure or the shape of the proximal probe array block is modified inorder to modify the electrostatic pattern that is presented by theproximal probe array block. In the example that is shown in FIG. 23,proximal probe array block 2302 has self-contained element 2314 that maybe controlled, e.g., by the components that are shown in FIG. 1, tochange the shape or the structure of proximal probe array block 2302. Asnoted above, the inter-probe gaps or spacings between the proximalprobes on a proximal probe array block may vary. In this example, aportion of the spacing or gap between a set of proximal probes isoccupied by self-contained element 2314. When controlled to do so,element 2314 expands or contracts, thereby increasing or decreasing theinter-probe gap or spacing between the set of proximal probes that arejuxtaposed to element 2314. As element 2314 expands, the juxtaposedproximal probes are moved, and the electrostatic pattern that ispresented by those probes is modified; in this example, a portion of theelectrostatic pattern is moved laterally. As the probes are moved, thecaptured molecule is manipulated.

Element 2314 may be a micro-mechanical structure, a nano-mechanicalstructure, or some other structure that is responsive to electroniccontrol. Alternatively, assuming that the conductive wires/leads to theproximal probes are insulated within the proximal probe array block,element 2314 may comprise electro-active polymers or otherelectro-active materials that stretch, contract, or otherwise changeshape or exhibit shape memory by the application of electric current tothe electro-active material. As the electro-active materials expand orcontract, the inter-probe gaps or spacings are enlarged or reduced,thereby providing flexibility in the substrate to match the structure ofa targeted molecule in order to capture the targeted molecule or tocause the desired manipulation of a captured molecule. In oneembodiment, multiple portions of the substrate of the proximal probearray block may comprise electro-active materials such that thedifferent portions are individually controllable.

With reference now to FIGS. 24A–24I, a set of diagrams depict multiplemolecular manipulations using a proximal probe array block in accordancewith an embodiment of the present invention. Although FIG. 13 depicts aflowchart in which a single loop through the flowchart represents aprocess for manipulating a single molecule, a sequence of multiplemanipulations may be performed in series; the sequence of manipulationsmay be performed by repeating steps 1302–1310 that are shown in FIG. 13,sometimes omitting step 1312 as necessary when it is not desired torelease a resulting molecule. FIGS. 24A–24I depicts an example of aseries of molecular manipulations in which time progresses from abeginning state as shown in FIG. 24A to an ending state in FIG. 24I.Individual proximal probes or their respective areas are not representedwithin FIGS. 24A–24I.

FIG. 24A depicts a beginning state of proximal probe array block 2402;electrostatic pattern 2404 on proximal probe array block 2402 isrepresented by an outline of a subset of proximal probes, some of whichpresent positive and negative electrostatic charges for capturing atarget molecule. It may be assumed that electrostatic pattern 2404 hascaptured a first target molecule that will be manipulated in subsequentfigures.

FIG. 24B depicts proximal probe array block 2402 at some later point intime; electrostatic pattern 2406 on proximal probe array block 2402represents an outline of another subset of proximal probes which may beassumed to have captured a second target molecule that will bemanipulated in subsequent figures.

FIG. 24C depicts proximal probe array block 2402 at some later point intime; electrostatic pattern 2408 on proximal probe array block 2402represents an outline of another subset of proximal probes. In thiscase, electrostatic pattern 2406 has been shifted in proximity withelectrostatic pattern 2404 to cause a chemical reaction between therespective first and second captured molecules to form a third capturedmolecule; electrostatic pattern 2408 is employed to hold the thirdcaptured molecule.

FIG. 24D depicts proximal probe array block 2402 at some later point intime; electrostatic pattern 2410 on proximal probe array block 2402represents an outline of another subset of proximal probes which may beassumed to have captured a fourth molecule that will be manipulated insubsequent figures. FIG. 24E depicts proximal probe array block 2402 atsome later point in time; electrostatic pattern 2410 on proximal probearray block 2402 has been moved and rotated to be in proximity withelectrostatic pattern 2408 to cause a chemical reaction between therespective third and fourth captured molecules to form a fifth capturemolecule, as shown in FIG. 24F in which electrostatic pattern 2412 isemployed to hold the fourth captured molecule.

FIG. 24G depicts proximal probe array block 2402 at some later point intime; a portion of electrostatic pattern 2412 as shown in FIG. 24F hasbeen shifted to form electrostatic pattern 2414 as shown in FIG. 24G. Inso doing, it may be assumed that the fourth captured molecule has beentwisted to some degree while being held by proximal probe array block2402. FIG. 24H depicts proximal probe array block 2402 at some laterpoint in time; a portion of electrostatic pattern 2414 as shown in FIG.24G has been split to form electrostatic pattern 2416 as shown in FIG.24H to prepare for the next molecular manipulation, which is shown at alater point in time in FIG. 24I. FIG. 24I depicts electrostatic pattern2418, which is a remaining portion of electrostatic pattern 2416 thathas been shifted and rotated; it may be assumed that the operations thatare shown in FIGS. 24G–24I have split the fourth captured molecule atsome desired location to form a fifth captured molecule. Proximal probearray block 2402 may hold the fifth captured molecule for someconfigurable period of time; the fifth captured molecule may be used ina subsequent molecular manipulation on proximal probe array block 2402,or the fifth captured molecule may undergo a chemical reaction with anuncaptured molecule within the reaction chamber that contains proximalprobe array block 2402 while being observable with detectors on proximalprobe array block 2402.

Hence, FIGS. 24A–24I illustrate a sequence of manipulations of multiplecaptured molecules at different points in time that results in thecreation of a complex molecule, thereby constructing a complex moleculethat might not be possible to construct using typical chemistry withfree-floating reagents in a typical reaction chamber. Another advantageof the present invention is the ability to make molecules that arerarely observed or observed with great difficulty in a typical reactionchamber. In some cases, it might be possible to create a molecule ofinterest in a typical reaction chamber, but because of a very low rateof reaction, once the molecule of interest is free-floating within thereaction chamber, it may be very difficult to target for a subsequentreaction. With the present invention, the molecule of interest can beconstructed and then held as a captured molecule in order to observe asubsequent reaction or to observe its general chemistry.

In a reverse fashion, a sequence of molecular manipulations may beperformed on a molecule to disassemble a molecule rather than toassemble a molecule as shown in FIGS. 24A–24I. In each step of thedisassembly procedure, a piece of a captured molecule may be removed,possibly with the help of one or more captured catalyst molecules thatare brought into contact with the captured molecule through molecularmanipulations.

The present invention may also be useful in analyzing the constituentpieces of a large molecule. For example, a large molecule might becreated on a proximal probe array block using the assembly process thatis shown in FIGS. 24A–24I. However, at the end of the procedure, thestructure of the captured molecule might be unknown; the capturedmolecule might be held by the proximal probe array block using a large,empirically discovered, electrostatic pattern even though the exactstructure of the captured molecule and its capture points might beunknown. By subjecting the large captured molecule to a series ofmolecular manipulations, smaller constituent pieces of the largecaptured molecule might be sequentially removed for subsequent analysis.The constituent pieces may then be shifted or otherwise moved to anisolated portion of the proximal probe array block or to anotherproximal probe array block, whereby the constituent pieces might be morereadily analyzed, possibly using additional molecular manipulations.After determining the structure of the constituent pieces, the structureof the larger, originating molecule might be discernible.

Although the figures depict a single arrangement of one or more proximalprobe array blocks for accomplishing a molecular manipulation or asequence of molecular manipulations as if a reaction chamber containedonly one such arrangement of proximal probe array blocks, it should benoted that multiple arrangements of proximal probe array blocks (mostlikely, identical arrangements of proximal probe array blocks) couldperform a sequence of molecular manipulations in parallel, therebygenerating multitudinous copies of one or more desired molecules. Iflarge numbers of such arrangements of proximal probe array blocks couldbe implemented, a large quantity of a desired molecule could bemanufactured. This large quantity of the desired molecule could then beused within conventional chemical reactions for a variety of purposes,such as for research, for industrial use, or for medicinal use.

Moreover, this embodiment of the present invention might be advantageousfor producing sufficient quantities of a molecule that might otherwisebe producible only in minute quantities with conventional chemistry.This embodiment of the present invention would be particularlyadvantageous in those cases in which minute quantities are too small tobe useful, e.g., for studying statistical properties of reactions thatinclude the molecule. In addition, the present invention might becost-effective for producing sufficient quantities of certain valuablemolecules that are otherwise cost-prohibitive to produce by conventionalchemistry.

The advantages of the present invention should be apparent in view ofthe detailed description that has been provided above. Linear, areal, orvolumed proximal probe array blocks can be fabricated by configuringproximal probes in one, two, or three dimensions, respectively. Theproximal probe array blocks can be used to accomplish complex chemistryor biology that would not be possible using conventional techniques.

For example, a scientist may desire to cut a long chain molecule at aspecific point. The scientist can target the chain molecule byprogramming the system of the present invention so that a proximal probearray block exhibits an electrostatic pattern that exerts electrostaticforces that attract the molecule's electrostatic properties that areinherently expressed by its molecular electron cloud. The proximal probearray block is then exposed to a liquid solution that contains thetargeted molecule. One of the targeted molecules eventually moves nearthe proximal probe array block by thermal motion, and the complementaryelectrostatic charges on the targeted molecule are attracted to theproximal probes, thereby enabling the targeted molecule to be capturedby the proximal probe array. Sensors on the proximal probe array blockcan detect the presence of the captured molecule, and the proximal probearray block can be used to manipulate the captured molecule in one ormore of a variety of manipulation actions. For example, portions of theelectrostatic pattern on the proximal probes can be shifted and/orrotated, thereby tearing the captured molecule at a specific chemicalbond within the capture molecule and producing two captured molecules.

In a similar manner, different portions of the proximal probe array maybe programmed to capture targeted molecules. The captured molecules aresubsequently shifted and rotated to specific positions and orientationson the proximal probe array so that the captured molecules are closeenough to engage in a chemical reaction that forms a new largermolecule, which is then released back into the liquid solution. In thismanner, exotic chemical manipulations can be performed with a devicethat is fabricated in accordance with an embodiment of the presentinvention.

Exotic biological manipulations can also be accomplished with thepresent invention. In living beings, most biological processes aredriven by DNA, RNA, other genetic molecules, and special proteins; allof these work on the principle of creating an electrostatic pattern ofcharges which closely match the complementary pattern of charges on themolecule to be manipulated. This causes the appropriate molecules to beattached to the enzyme, catalyst, or other molecule. In some instances,the molecules are cut, or the molecules are attached to other moleculesby holding them together or by bending them apart. In the past,extremely laborious experiments would have to be carried out with manyknown catalysts, enzymes, etc., to discover one that performs thedesired molecular manipulations, which may require many years of work.In addition, genetic techniques have been used to find genes which codefor specific molecular transformations or functions, after whichbacteria are engineered with the genes to produce chemicals that performthe desired molecular transformations or functions; this is alsoextremely laborious work.

The present invention provides programmable processes and programmablestructures for accomplishing similar biological activities; for example,a captured molecule can act as an enzyme or a catalyst while themolecule remains captured by a proximal probe array. A scientist canprogram a desired molecular manipulation via electronic hardware, whichcan potentially eliminate the extremely laborious work. Furthermore, thepresent invention may be useful for testing for the presence ofdiseases, genes that predispose a person to certain problems, drugs,pollutants, viruses, bacteria, or other substances in blood or otherbodily fluids. Inactive or non-threatening versions of disease-inducingmolecules can be manufactured and introduced back into the body to thatan immune system can create antibodies against the original harmfulmolecule. In addition, the present invention may be used to accomplishmolecular manipulations that fold a molecular, particularly biologicalmolecules, such as proteins. For example, amino acid chains coded by DNAcan fold themselves in many different ways, and organisms usually havemechanisms to destroy or undo misfolded proteins. However, using thisdevice, one would be able to force folding of such molecules toparticular shapes in order to study the effects of such foldings or toobtain molecules that are either too difficult or not possible to obtainthrough natural biological processes.

It is important to note that while the present invention has beendescribed such that it may be part of a data processing system; those ofordinary skill in the art will appreciate that some of the processes ofthe present invention are capable of being distributed in the form ofinstructions in a computer readable medium and a variety of other forms,regardless of the particular type of signal bearing media actually usedto carry out the distribution. Examples of computer readable mediainclude media such as EPROM, ROM, tape, paper, floppy disc, hard diskdrive, RAM, and CD-ROMs and transmission-type media, such as digital andanalog communications links.

A method is generally conceived to be a self-consistent sequence ofsteps leading to a desired result. These steps require physicalmanipulations of physical quantities. Usually, though not necessarily,these quantities take the form of electrical or magnetic signals capableof being stored, transferred, combined, compared, and otherwisemanipulated. It is convenient at times, principally for reasons ofcommon usage, to refer to these signals as bits, values, parameters,items, elements, objects, symbols, characters, terms, numbers, or thelike. It should be noted, however, that all of these terms and similarterms are to be associated with the appropriate physical quantities andare merely convenient labels applied to these quantities.

The description of the present invention has been presented for purposesof illustration but is not intended to be exhaustive or limited to thedisclosed embodiments. Many modifications and variations will beapparent to those of ordinary skill in the art. The embodiments werechosen to explain the principles of the invention and its practicalapplications and to enable others of ordinary skill in the art tounderstand the invention in order to implement various embodiments withvarious modifications as might be suited to other contemplated uses.

1. A method for manipulating a molecule, the method comprising: placingan electrostatic pattern on a subset of two or more proximal probes in aset of proximal probes; capturing a molecule using electrostatic forcesthat are exerted by the electrostatic pattern; and manipulating themolecule while the molecule remains captured by the set of proximalprobes.
 2. The method of claim 1 further comprising: applying anelectric potential to a conductive material in each proximal probe inthe subset of proximal probes such that an end portion of each proximalprobe in the subset of proximal probes exerts an electrostatic force. 3.The method of claim 1 further comprising: independently controlling eachproximal probe in the subset of proximal probes such that each proximalprobe in the subset of proximal probes is able to exert an electrostaticforce strength that is unique among the subset of proximal probes. 4.The method of claim 1 further comprising: modifying the electro staticpattern to create a different electrostatic pattern on a differentsubset of two or more proximal probes in the set of proximal probes suchthat the molecule moves and/or rotates over the set of proximal probeswhile the molecule remains captured by the set of proximal probes. 5.The method of claim 1 further comprising: modifying the electrostaticpattern to bend the molecule while the molecule remains captured by theset of proximal probes.
 6. The method of claim 1 further comprising:modifying the electrostatic pattern to split the molecule into a firstmolecule and a second molecule.
 7. The method of claim 6 furthercomprising: continuing to hold the first molecule or the second moleculeby the set of proximal probes; and manipulating the first molecule orthe second molecule with the set of proximal probes.
 8. The method ofclaim 1 further comprising: modifying the electrostatic pattern tocreate a first electrostatic pattern on a first subset of two or moreproximal probes in the set of proximal probes and a second electrostaticpattern on a second subset of two or more proximal probes in the set ofproximal probes.
 9. The method of claim 8 further comprising:manipulating the first electrostatic pattern and the secondelectrostatic pattern independently.
 10. The method of claim 8 furthercomprising: acting independently on a first portion of the molecule withthe first electrostatic pattern and on a second portion of the moleculewith the second electrostatic pattern.
 11. The method of claim 1 whereinthe subset of two or more proximal probes in a set of proximal probesrepresents a first subset of proximal probes, wherein the electrostaticpattern represents a first electrostatic pattern, and wherein themolecule represents a first molecule, further comprising: placing anelectrostatic pattern on a second subset of two or more proximal probesin the set of proximal probes, wherein the first subset and the secondsubset do not intersect capturing a second molecule using electrostaticforces that are exerted by the second electrostatic pattern; andmanipulating the second molecule while the second molecule remainscaptured by the set of proximal probes.
 12. The method of claim 11further comprising: manipulating the first molecule and the secondmolecule independently while the first molecule and the second moleculeremain captured by the set of proximal probes.
 13. The method of claim11 further comprising: moving the first molecule into close proximitywith the second molecule while the first molecule and the secondmolecule remain captured by the set of proximal probes; and causing achemical reaction between the first molecule and the second molecule.14. The method of claim 13 further comprising: forming a third moleculefrom at least a portion of the first molecule and at least a portion ofthe second molecule.
 15. The method of claim 1 wherein two or moreproximal probes in the set of proximal probes include a cantileveredstructure.
 16. The method of claim 15 wherein each proximal probe in thesubset of proximal probes includes a cantilevered structure, furthercomprising: flexing independently at least two of the proximal probes inthe subset of proximal probes to bend the molecule while the moleculeremains captured by the set of proximal probes.
 17. The method of claim15 wherein each proximal probe in the subset of proximal probes includesa cantilevered structure, further comprising: flexing independently atleast two of the proximal probes in the subset of proximal probes tosplit the molecule into a first molecule and a second molecule.
 18. Themethod of claim 17 further comprising: continuing to hold the firstmolecule or the second molecule by the set of proximal probes; andmanipulating the first molecule or the second molecule with the set ofproximal probes.
 19. The method of claim 1 further comprising: using themolecule in a chemical reaction while the molecule remains captured bythe set of proximal probes.
 20. The method of claim 1 furthercomprising: using the molecule as a catalyst in a chemical reactionwhile the molecule remains captured by the set of proximal probes. 21.The method of claim 1 further comprising: using the molecule as anenzyme in a biological reaction while the molecule remains captured bythe set of proximal probes.
 22. The method of claim 1 wherein a firstset of proximal probes are physically connected as a first entity and asecond set of proximal probes are physically connected as a secondentity such that the first entity and the second entity can beindependently manipulated.
 23. The method of claim 22 furthercomprising: holding the captured molecule by the first entity and thesecond entity simultaneously.
 24. The method of claim 23 furthercomprising: manipulating the first entity while time second entityrennins stationary.
 25. The method of claim 24 further comprising:bending the molecule while the molecule remains captured by the set ofproximal probes.
 26. The method of claim 24 further comprising:splitting the molecule into a first molecule and a second molecule. 27.The method of claim 1 further comprising: repeatedly manipulating atleast a portion of the molecule while at least a portion of the moleculeremains captured by the set of proximal probes.
 28. The method of claim27 further comprising: creating a new molecule that includes the portionof the molecule through a sequence of manipulations that includes theportion of the molecule.
 29. The method of claim 28 further comprising:assembling the new molecule by adding portions of other molecules to theportion of the molecule.
 30. The method of claim 28 further comprising:disassembling the molecule by removing portions of the molecule.
 31. Themethod of claim 1 further comprising: manipulating the molecule to foldthe molecule.
 32. The method of claim 31 wherein the molecule is aprotein.
 33. The method of claim 1 wherein the molecule is a piece of adeoxyribonucleic acid (DNA) molecule.
 34. The method of claim 1 whereinthe molecule is a genetic molecule.
 35. An apparatus for manipulating amolecule, the apparatus comprising: means for placing an electrostaticpattern on a subset of two or more proximal probes in a set of proximalprobes; means for capturing a molecule using electrostatic forces thatare exerted by the electrostatic pattern; and means for manipulating themolecule while the molecule remains captured by the set of proximalprobes.
 36. The apparatus of claim 35 further comprising: means forapplying an electric potential to a conductive material in each proximalprobe in the subset of proximal probes such that an end portion of eachproximal probe in die subset of proximal probes exerts an electrostaticforce.
 37. The apparatus of claim 35 further comprising: means forindependently controlling each proximal probe in the subset of proximalprobes such that each proximal probe in the subset of proximal probes isable to exert an electrostatic force strength that is unique among thesubset of proximal probes.
 38. The apparatus of claim 35 furthercomprising: means for modifying the electrostatic pattern to create adifferent electrostatic pattern on a different subset of two or moreproximal probes in the set of proximal probes such that the moleculemoves and/or rotates over the set of proximal probes while the moleculeremains captured by the set of proximal probes.
 39. The apparatus ofclaim 35 further comprising: means for modifying the electrostaticpattern to bend the molecule while the molecule remains cap aired by theset of proximal probes.
 40. The apparatus of claim 35 furthercomprising: means for modifying the electrostatic pattern to split themolecule into a first molecule and a second molecule.
 41. The apparatusof claim 40 further comprising: means for continuing to hold the firstmolecule or the second molecule by the set of proximal probes; and meansfor manipulating the first molecule or the second molecule with the setof proximal probes.
 42. The apparatus of claim 35 further comprising:means for modifying the electrostatic pattern to create a firstelectrostatic pattern on a first subset of two or more proximal probesin the set of proximal probes and a second electrostatic pattern on asecond subset of two or more proximal probes in the set of proximalprobes.
 43. The apparatus of claim 42 further comprising: means formanipulating the first electrostatic pattern and the secondelectrostatic pattern independently.
 44. The apparatus of claim 42further comprising: means for acting independently on a first portion ofthe molecule with the first electrostatic pattern and on a secondportion of the molecule with the second electrostatic pattern.
 45. Theapparatus of claim 35 wherein the subset of two or more proximal probesin a set of proximal probes represents a first subset of proximalprobes, wherein the electrostatic pattern represents a firstelectrostatic pattern, and wherein the molecule represents a firstmolecule, further comprising: means for placing an electrostatic patternon a second subset of two or more proximal probes in the set of proximalprobes, wherein the first subset and the second subset do not intersect;means for capturing a second molecule using electrostatic forces thatare exerted by the second electrostatic pattern; and means formanipulating the second molecule while the second molecule remainscaptured by the set of proximal probes.
 46. The apparatus of claim 45further comprising: means for manipulating the first molecule and thesecond molecule independently while the first molecule and the secondmolecule remain captured by the set of proximal probes.
 47. Apparatus ofclaim 45 further comprising: means for moving the first molecule intoclose proximity with the second molecule while the first molecule andthe second molecule remain captured by the set of proximal probes; andmeans for causing a chemical reaction between the first molecule and thesecond molecule.
 48. The apparatus of claim 47 tether comprising: meansfor forming a third molecule from at least a portion of the firstmolecule and at least a portion of the second molecule while the thirdmolecule.
 49. The apparatus of claim 35 wherein two or more proximalprobes in the set of proximal probes include a cantilevered structure.50. The apparatus of claim 49 wherein each proximal probe in the subsetof proximal probes includes a cantilevered structure, furthercomprising: means for flexing independently at least two of the proximalprobes in the subset of proximal probes to bend the molecule while themolecule remains captured by the set of proximal probes.
 51. Theapparatus of claim 49 wherein each proximal probe in the subset ofproximal probes includes a cantilevered structure, further comprising:means for flexing independently at least two of the proximal probes inthe subset of proximal probes to split the molecule into a firstmolecule and a second molecule.
 52. The apparatus of claim 51 furthercomprising: means for continuing to hold the first molecule or thesecond molecule by the set of proximal probes; and means formanipulating the first molecule or the second molecule with the set ofproximal probes.
 53. The apparatus of claim 35 further comprising: meansfor using the molecule in a chemical reaction while the molecule remainscaptured by the set of proximal probes.
 54. The apparatus of claim 35further comprising: means for using the molecule as a catalyst in achemical reaction while the molecule remains captured by the set ofproximal probes.
 55. The apparatus of claim 35 further comprising: meansfor using the molecule as an enzyme in a biological reaction while themolecule remains captured by the set of proximal probes.
 56. Theapparatus of claim 35 wherein a first set of proximal probes arephysically connected as a first entity and a second set of proximalprobes are physically connected as a second entity such that the firstentity and the second entity can be independently manipulated.
 57. Theapparatus of claim 56 further comprising: means for holding the capturedmolecule by the first entity and the second entity simultaneously. 58.The apparatus of claim 57 further comprising: means for manipulating thefirst entity while the second entity remains stationary.
 59. Theapparatus of claim 58 further comprising: means for bending the moleculewhile the molecule remains captured by the set of proximal probes. 60.The apparatus of claim 58 further comprising: means for splitting themolecule into a first molecule and a second molecule.
 61. The apparatusof claim 35 further comprising: means for repeatedly manipulating atleast a portion of the molecule while at least a portion of the moleculeremains captured by the set of proximal probes.
 62. The apparatus ofclaim 61 further comprising: means for creating a new molecule thatincludes the portion of the molecule through a sequence of manipulationsthat includes the portion of the molecule.
 63. The apparatus of claim 62further comprising: means for assembling the new molecule by addingportions of other molecules to the portion of the molecule.
 64. Theapparatus of claim 62 further comprising: means for disassembling themolecule by removing portions of the molecule.
 65. The apparatus ofclaim 35 wherein the means for manipulating the molecule comprises meansfor folding the molecule.
 66. The apparatus of claim 35 wherein themolecule is a protein.
 67. The apparatus of claim 35 wherein themolecule is a piece of a deoxyribonucleic acid (DNA) molecule.